Gefapixant
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MedKoo CAT#: 561852

CAS#: 1015787-98-0 (free base)

Description: Gefapixant, also known as AF-219 or MK-7264, is a P2X3 receptor antagonist. Gefapixant is currently under clinical trials for chronic cough. It is believed that excessive activation of P2X3 receptors is associated with hyper-sensitization of sensory neurons. Neuronal hyper-sensitization in the airways and lungs, triggered by injury or infection, can cause an exaggerated, persistent and frequent urge to cough, so called chronic cough. P2X3 receptors seem to have a key role in mediation of cough neuronal hypersensitivity. Antagonists of P2X3 receptors such as AF-219 are a promising new group of antitussives.

Chemical Structure

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Gefapixant
CAS# 1015787-98-0 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 561852
Name: Gefapixant
CAS#: 1015787-98-0 (free base)
Chemical Formula: C14H19N5O4S
Exact Mass: 353.12
Molecular Weight: 353.397
Elemental Analysis: C, 47.58; H, 5.42; N, 19.82; O, 18.11; S, 9.07

Price and Availability

Size Price Availability Quantity
25mg USD 450 2 Weeks
50mg USD 750 2 Weeks
100mg USD 1250 2 Weeks
200mg USD 2050 2 Weeks
500mg USD 3250 2 Weeks
1g USD 4650 2 Weeks
2g USD 6450 2 Weeks
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Related CAS #: 2310299-91-1 (citrate)   1015787-98-0 (free base)    

Synonym: Gefapixant; MK-7264; MK 7264; MK7264; AF-219; AF219; AF 219; RO4926219; RO-4926219; RO 4926219;

IUPAC/Chemical Name: 5-[(2,4-diaminopyrimidin-5-yl)oxy]-2-methoxy-4-(propan-2-yl)benzene-1-sulfonamide

InChi Key: HLWURFKMDLAKOD-UHFFFAOYSA-N

InChi Code: InChI=1S/C14H19N5O4S/c1-7(2)8-4-10(22-3)12(24(17,20)21)5-9(8)23-11-6-18-14(16)19-13(11)15/h4-7H,1-3H3,(H2,17,20,21)(H4,15,16,18,19)

SMILES Code: O=S(C1=CC(OC2=CN=C(N)N=C2N)=C(C(C)C)C=C1OC)(N)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: Gefapixant is an orally active and potent purinergic P2X3 receptor (P2X3R) antagonist, with IC50 values of ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors.
In vitro activity: Antagonism of human P2X3 receptors using a submaximal MK‐7264 concentration (300 nM; approximate IC70) was not surmounted by increasing the concentration of α,β‐meATP agonist (Figure 1e), indicating that MK‐7264 acts independently of agonist concentration to block P2X3. In addition to suppression of response maxima, MK‐7264 also significantly reduced α,β‐meATP potency (EC50 1.0 ± 0.1 μM vehicle vs. 6.0 ± 1.5 μM with 300‐nM MK‐7264; N = 5, paired sample t test P < .05). These data suggest that MK‐7264 is a negative allosteric modulator of the human P2X3 receptor. Reference: Br J Pharmacol. 2019 Jul;176(13):2279-2291. https://pubmed.ncbi.nlm.nih.gov/30927255/
In vivo activity: Withdrawal threshold was 13.3 ± 0.2 g (N = 20) in naïve control rats. MK‐7264 was also efficacious in reducing weight‐bearing discomfort at 1 and 3 hr after dosing (Figure 4b). The maximum effect of MK‐7264 (30 mg·kg−1) was observed at 3 hr and similar to that of naproxen (20 mg·kg−1), where difference in weight bearing between contralateral and ipsilateral limbs was 55 ± 6 g, 35 ± 4 g, and 34 ± 4 g for vehicle control, MK‐7264, and naproxen (N = 10; P < .05 for all treatments vs. vehicle control), respectively. Reference: Br J Pharmacol. 2019 Jul;176(13):2279-2291. https://pubmed.ncbi.nlm.nih.gov/30927255/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 38.0 107.53

Preparing Stock Solutions

The following data is based on the product molecular weight 353.40 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Richards D, Gever JR, Ford AP, Fountain SJ. Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. Br J Pharmacol. 2019 Jul;176(13):2279-2291. doi: 10.1111/bph.14677. Epub 2019 May 11. PMID: 30927255; PMCID: PMC6555852.
In vitro protocol: 1. Richards D, Gever JR, Ford AP, Fountain SJ. Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. Br J Pharmacol. 2019 Jul;176(13):2279-2291. doi: 10.1111/bph.14677. Epub 2019 May 11. PMID: 30927255; PMCID: PMC6555852.
In vivo protocol: 1. Richards D, Gever JR, Ford AP, Fountain SJ. Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. Br J Pharmacol. 2019 Jul;176(13):2279-2291. doi: 10.1111/bph.14677. Epub 2019 May 11. PMID: 30927255; PMCID: PMC6555852.

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1: Wang J, Wang Y, Cui WW, Huang Y, Yang Y, Liu Y, Zhao WS, Cheng XY, Sun WS, Cao P, Zhu MX, Wang R, Hattori M, Yu Y. Druggable negative allosteric site of P2X3 receptors. Proc Natl Acad Sci U S A. 2018 May 8;115(19):4939-4944. doi: 10.1073/pnas.1800907115. Epub 2018 Apr 19. PubMed PMID: 29674445; PubMed Central PMCID: PMC5948998.

2: Burnstock G. The therapeutic potential of purinergic signalling. Biochem Pharmacol. 2018 May;151:157-165. doi: 10.1016/j.bcp.2017.07.016. Epub 2017 Jul 21. Review. PubMed PMID: 28735873.

3: Sheridan C. Merck stakes out 'irritable' neuron territory with $1.25 billion. Nat Biotechnol. 2016 Sep 8;34(9):900. doi: 10.1038/nbt0916-900. PubMed PMID: 27606448.

4: Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015 Mar 28;385(9974):1198-205. doi: 10.1016/S0140-6736(14)61255-1. Epub 2014 Nov 25. PubMed PMID: 25467586.

5: Morice AH. Developing antitussives the clinician's pipeline-what do we need? J Thorac Dis. 2014 Oct;6(Suppl 7):S735-8. doi: 10.3978/j.issn.2072-1439.2014.08.40. Review. PubMed PMID: 25383208; PubMed Central PMCID: PMC4222922.

6: Ochoa-Cortes F, Liñán-Rico A, Jacobson KA, Christofi FL. Potential for developing purinergic drugs for gastrointestinal diseases. Inflamm Bowel Dis. 2014 Jul;20(7):1259-87. doi: 10.1097/MIB.0000000000000047. Review. PubMed PMID: 24859298; PubMed Central PMCID: PMC4340257.

7: Ford AP, Undem BJ. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Front Cell Neurosci. 2013 Dec 19;7:267. doi: 10.3389/fncel.2013.00267. Review. PubMed PMID: 24391544; PubMed Central PMCID: PMC3867694.